Osteoporosis is a 'silent' progressive and debilitating disease characterized by bone loss, thinning cortical bone and disorganized trabecular bone leading to bone fragility and fracture. Osteoporosis results when the processes of bone formation and bone resorption become uncoupled and the rate of bone resorption becomes much greater than that of bone formation. FDA-approved pharmaceutical interventions have antiresorptiive properties. Some of these drugs have serious side effects. Fluoride (F) therapy as sodium fluoride is the only one shown to consistently increase bone mass, but was also reported to increase fracture risk. The goal of the proposed research is to develop novel materials incorporating magnesium (Mg), zinc (Zn), F ions in a calcium (Ca) phosphate system (Mg/Zn/F-BCP). Separately, these ions have been associated with bone formation, biomineralization and osteoporosis therapy. Specific aims are to: (1) prepare and characterize the crystallographic, morphologic, and chemical properties of a series of Mg/Zn/F-BCP materials; (2) determine the short and long term initial dissolution rates and release of Ca, Mg, Zn, P and F ions of the materials prepared in Aim 1; (3) determine in vitro response of bone forming (osteoblasts) and bone resorbing (osteoclasts) cells to Mg/Zn/F-BCPs of various compositions using human osteoblast-like cells and rat osteoclast-like cells; (4) determine the effect of orally administered various Mg/Zn/F-BCPs on (a) bone properties (mechanical strength, density, quality, composition, and histomorphometric parameters and bone mineral (crystallinity, composition and dissolution) of adult and aged female and male rats; and (b) on the development of osteoporosis (deficient-diet induced) in adult rats; and (5) determine therapeutic effect of various injected Mg/Zn/F-BCPs on ovariectomized rats using biomechanical, histomorphometric measurements and chemical analyses on bone and plasma analyses. Hypothesis: Biomaterials with Zn, Mg and F ions in a calcium phosphate matrix (used as dietary supplement and ion releasing injectible 'implants') will improve bone health.